Cailliez, M. et al. Anakinra is safe and effective in controlling hyperimmunoglobulinaemia D syndrome-associated febrile crisis. J. Inherit. Metab. Dis. 29, 763

Hôpital Bicêtre (Hôpitaux Universitaires Paris-Sud), Lutetia Parisorum, Île-de-France, France
Journal of Inherited Metabolic Disease (Impact Factor: 3.37). 01/2007; 29(6):763. DOI: 10.1007/s10545-006-0408-7
Source: PubMed


Hyper-IgD and periodic fever syndrome (HIDS) is a hereditary autoinflammatory syndrome, characterized by recurrent inflammatory attacks. Treatment of HIDS is difficult. Recently, the IL-1ra analogue anakinra was reported to be successful in aborting the IgD inflammatory attacks in a vaccination model. We report a clinical case of spectacular reduction of febrile attacks in a severe HIDS patient.

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    • "Anti-TNF therapy (Etanercept) has been found to reduce the frequency and intensity of fever attacks in some patients (66–68) but not in others (69). In the same line a positive response was also observed after the use of Anakinra (70–72). The same variable response was also observed in the International HIDS registry (63). "
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    ABSTRACT: Inherited autoinflammatory diseases are secondary to mutations of proteins playing a pivotal role in the regulation of the innate immunity leading to seemingly unprovoked episodes of inflammation. The understanding of the molecular pathways involved in these disorders has shed new lights on the pattern of activation and maintenance of the inflammatory response and disclosed new molecular therapeutic targets. Cryopyrin-associated periodic syndrome (CAPS) represents the prototype of an autoinflammatory disease. The study of the pathophysiological consequence of mutations in the cryopyrin gene (NLRP3) allowed the identification of intracellular pathways responsible for the activation and secretion of the potent inflammatory cytokine interleukin-1β (IL-1β). It became clear that several multi-factorial inflammatory conditions display a number of pathogenic and clinical similarities with inherited autoinflammatory diseases. The dramatic effect of interleukin-1 (IL-1) blockade in CAPS opened new perspectives for the treatment of other inherited and multi-factorial autoinflammatory disorders. Several IL-1 blockers are now available on the market. In this review we outline the more recent novelties in the treatment with different IL-1 blockers in inherited and multi-factorial autoinflammatory diseases.
    Full-text · Article · Oct 2013 · Frontiers in Immunology
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    • "These observations permitted to hypothesize that an increase in temperature may be involved in triggering the attacks [10]. Although in the last decade the knowledge of MKD pathogenesis has increased, an etiologic treatment for MKD is still unavailable, and anti-inflammatory drugs [11] as well as novel biologic treatments [12] [13] are currently used with different and debatable results. We recently showed that plant isoprenoids (such as geraniol ) [14] and inhibitors of farnesylation (such as Tipifarnib) [15] could reverse the inflammatory response in cellular and animal MKD models [16]. "
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    ABSTRACT: Mevalonate Kinase Deficiency (MKD) is a rare autosomal recessive inborn disorder of cholesterol biosynthesis caused by mutations in the mevalonate kinase (MK) gene, leading to MK enzyme decreased activity. The consequent shortage of mevalonate-derived isoprenoid compounds results in an inflammatory phenotype, caused by the activation of the NALP3 inflammasome that determines an increased caspase-1 activation and IL-1 β release. In MKD, febrile temperature can further decrease the residual MK activity, leading to mevalonate pathway modulation and to possible disease worsening. We previously demonstrated that the administration of exogenous isoprenoids such as geraniol or the modulation of the enzymatic pathway with drugs, such as Tipifarnib, partially rescues the inflammatory phenotype associated with the defective mevalonic pathway. However, it has not been investigated yet how temperature can affect the success of these treatments. Thus, we investigated the effect of temperature on primary human monocytes from MKD patients. Furthermore the ability of geraniol and Tipifarnib to reduce the abnormal inflammatory response, already described at physiological temperature in MKD, was studied in a febrile condition. We evidenced the role of temperature in the modulation of the inflammatory events and suggested strongly considering this variable in future researches aimed at finding a treatment for MKD.
    Full-text · Article · Sep 2013
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    • "Anti-IL-1 and anti-TNF-α agents are reasonable therapeutic alternatives for patients with MKD, as IL-1 and TNF-α seem to play a relevant role in acute inflammatory attacks of MKD [114]. With regard to anti-IL-1 agents, the frequency and severity of fever attacks were eliminated or significantly reduced by anakinra treatment in most cases, demonstrating that most symptoms of MKD might be controlled or at least attenuated by anakinra [111, 115–118]. "
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    ABSTRACT: Treatment of monogenic autoinflammatory disorders, an expanding group of hereditary diseases characterized by apparently unprovoked recurrent episodes of inflammation, without high-titre autoantibodies or antigen-specific T cells, has been revolutionized by the discovery that several of these conditions are caused by mutations in proteins involved in the mechanisms of innate immune response, including components of the inflammasome, cytokine receptors, receptor antagonists, and oversecretion of a network of proinflammatory molecules. Aim of this review is to synthesize the current experience and the most recent evidences about the therapeutic approach with biologic drugs in pediatric and adult patients with monogenic autoinflammatory disorders.
    Full-text · Article · Jul 2013 · Mediators of Inflammation
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